O'Neill T P, Haigler H J
Brain Res. 1985 Feb 18;327(1-2):97-103. doi: 10.1016/0006-8993(85)91503-3.
When norepinephrine was applied microiontophoretically to certain neurons in the pontine reticular formation of rats, it produced an increase in neuronal firing like that produced by noxious stimulation. Previous studies have shown that both noxious stimulus- and norepinephrine-evoked increases in neuronal firing are mediated by alpha-adrenoceptors. These neurons were unresponsive to non-noxious stimuli, suggesting that they might play a role in nociception. Microiontophoretic or systemic administration of the selective alpha 2-adrenoceptor agonist clonidine significantly attenuated noxious stimulus-evoked firing, but had little effect on firing evoked by norepinephrine. This effect of clonidine could be prevented by the alpha 2-adrenoceptor antagonists piperoxan and yohimbine. These antagonists, when given alone, increased noxious stimulus-evoked firing, but had no effect on firing evoked by norepinephrine. In contrast, the selective alpha 1-adrenoceptor antagonist ARC-239 (2-(2,4-(o-methoxyphenyl)-piperazin-1-yl)ethyl-4,4-dimethyl-1,3-(2 H,4) isoquinolindione dihydrochloride) attenuated both noxious stimulus- and norepinephrine-evoked firing. These data are consistent with the hypothesis that presynaptic alpha 2-adrenoceptors modulate the release of norepinephrine. Furthermore, these data suggest that the pontine reticular formation is one site at which clonidine could act to produce analgesia.
当将去甲肾上腺素以微量离子透入法施加于大鼠脑桥网状结构的某些神经元时，它会使神经元放电增加，就如同由伤害性刺激所产生的那样。先前的研究表明，伤害性刺激和去甲肾上腺素诱发的神经元放电增加均由α-肾上腺素能受体介导。这些神经元对非伤害性刺激无反应，这表明它们可能在痛觉感受中发挥作用。微量离子透入法或全身性给予选择性α₂-肾上腺素能受体激动剂可乐定可显著减弱伤害性刺激诱发的放电，但对去甲肾上腺素诱发的放电影响很小。可乐定的这种作用可被α₂-肾上腺素能受体拮抗剂哌罗克生和育亨宾所阻断。这些拮抗剂单独给药时，会增加伤害性刺激诱发的放电，但对去甲肾上腺素诱发的放电无影响。相比之下，选择性α₁-肾上腺素能受体拮抗剂ARC-239（2-(2,4-(邻甲氧基苯基)-哌嗪-1-基)乙基-4,4-二甲基-1,3-(2H,4)异喹啉二酮二盐酸盐）可减弱伤害性刺激和去甲肾上腺素诱发的放电。这些数据与突触前α₂-肾上腺素能受体调节去甲肾上腺素释放的假说一致。此外，这些数据表明脑桥网状结构是可乐定可能发挥镇痛作用的一个部位。
